Transforming growth factor beta 1 gene transcription in infection and severe sepsis displays distinguishing characteristics

Introduction

Transforming growth factor beta (TGFβ) is a pleotrophic cytokine that promotes a CD4 Th1 response to infection. We examined the gene expression of TGFβ by quantitative RT-PCR in three study groups: 10 healthy controls, 15 patients with Gram-negative bacteraemia but without severe sepsis, and 58 patients with severe sepsis.

Methods

Blood samples were collected from healthy controls at one time point. In bacteraemic patients, blood sampling was carried out within 24 hours of the positive blood culture being reported. In 58 patients presenting with severe sepsis, blood sampling was carried on day 1 of intensive care admission and on day 7 in survivors. Mononuclear cells were isolated and TGFβ mRNA was quantified using the technique of quantitative QRT-PCR. All values are stated as the median and interquartile range. Between-group comparisons were performed by Wilcoxon rank sum test.

Results

TGFβ mRNA copy numbers were significantly reduced in the bacteraemic group (1.99 × 10⁶; 2.22 × 10⁶–1.92 × 10⁶) compared with controls (3.8 × 10⁶; 4.1 × 10⁶–2.9 × 10⁶), P = 0.01, and was significantly reduced in the sepsis group (1.97 × 10⁶; 2.8 × 10⁶–0.76 × 10⁶) compared with the control group, P = 0.009. While median TGFβ copy numbers were similar in sepsis and bacteraemia groups, 18 of 58 (30%) patients with sepsis had TGFβ copy numbers less than the lowest of the bacteraemic group (P = 0.02). In the sepsis group, 19 patients died. There was no association between TGFβ mRNA copy numbers and outcome measures such as mortality, the presence of shock after prolonged sepsis, duration of vasopressor support, duration of mechanical ventilation and duration of intensive care stay.

Conclusion

The human host response to infection is related to a distinct pattern of TGFβ gene transcription, with deficient TGFβ gene transcription related to the occurrence of infection and onset of septic shock rather than recovery from a shocked state or survival. This information could be used to structure genomic studies in sepsis and infection.